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(Circulation. 2005;111:2257-2273.)
© 2005 American Heart Association, Inc.

Basic Science for Clinicians

Molecular Basis of Restenosis and Drug-Eluting Stents

Marco A. Costa, MD, PhD; Daniel I. Simon, MD

From the Division of Cardiology & Cardiovascular Imaging Core Laboratories, University of Florida, Shands-Jacksonville, Jacksonville, Fla (M.A.C.), and the Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (D.I.S.).

Correspondence to Daniel I. Simon, MD, Cardiovascular Division, 75 Francis St, Tower 3, Boston, MA 02115. E-mail dsimon@rics.bwh.harvard.edu

Key Words: stents • restenosis • inflammation • prevention • cells

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 

Resolution of restenosis probably requires both creation of the largest possible residual lumen and substantial inhibition of intimal hyperplasia.

— J.S. Forrester and coworkers¹

Dr Forrester’s prediction that resolution of restenosis would require the translational merging of molecular mechanisms of proliferation with local scaffolding and drug-delivery devices appears to have been remarkably prescient. The application of drug-eluting stent (DES) technology to improve clinical outcomes after percutaneous coronary intervention (PCI) represents one of the greatest success stories in cardiology. This review highlights the molecular basis of restenosis and DES for the clinical and interventional cardiologist and vascular biologist.

	Restenosis: Definitions and Mechanisms

 
Restenosis is the arterial wall’s healing response to mechanical injury and comprises 2 main processes—neointimal hyperplasia (ie, smooth muscle migration/proliferation, extracellular matrix deposition) and vessel remodeling. Primarily on the basis of observations from animal studies, Forrester and coworkers¹ proposed a paradigm for neointimal hyperplasia as a general wound-healing response. Platelet aggregation, inflammatory cell infiltration, release of growth factors, medial smooth muscle cell (SMC) modulation and proliferation, proteoglycan deposition, and extracellular matrix remodeling were identified as the major milestones in the temporal sequence of this response. This view of the neointimal hyperplasia process was modified subsequently by Libby and colleagues² to reconcile certain important clinical features—namely, that thrombosis, often invoked as a cause of SMC proliferation, wanes before intimal thickening peaks and that antithrombotic therapy failed to eliminate restenosis. In this cascade model, a special case was made for the centrality of inflammation, and it was proposed that autocrine or paracrine mediators (eg, . . . [Full Text of this Article]

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